Early detection of bone metabolism changes under different antiepileptic drugs (ED-BoM-AED)--a prospective multicenter study

Abstract

Purpose: To determine early changes in bone turnover markers induced by treatment with oxcarbazepine or valproate.

Methods: In this prospective study, 31 adults with newly diagnosed epilepsy were included who were started on therapy with either oxcarbazepine (OXC, n=16, mean age 45.6 years, 37.5% female) or valproate (VPA, n=15, mean age 42.2 years, 33.3% female). Clinical characteristics were obtained at baseline, after 2 weeks and 3 months. In addition, blood samples were drawn at each visit. Calcium, phosphate, alkaline phosphatase (AP), receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), osteocalcin (OC) and cathepsin K were determined.

Results: In OXC treated patients, OPG increased by 0.06 pmol/L (p=0.0004) after 2 weeks and remained elevated by 0.05 pmol/L (p=0.02) after 3 months. Between 2 weeks and 3 months of OXC treatment, OC increased by 1.98 ng/mL (p=0.02). During the first 3 months of OXC treatment, total serum AP increased by 11%±9% (p=0.02). Compared to baseline, serum calcium raised by 0.06 mmol/L (p=0.04) after 2 weeks and by 0.07 mmol/L (p=0.004) after 3 months of OXC treatment. In VPA treated patients, a late OPG increase by 0.07 pmol/L (p=0.007) occurred after 3 months. During the first 3 months of OXC treatment, total serum AP decreased by by 7%±15% (p=0.03). No changes in OC or calcium were seen. RANKL was below detection limit in 16 out of 31 patients (52%) and did not change significantly during treatment. Cathepsin K was below detection limit at baseline in 27 out of 31 patients (87%) and was therefore not further evaluated. Phosphate did not change during treatment.

Conclusion: Increased bone turnover can be measured within few weeks of newly started treatment with OXC, while significant changes under VPA treatment occurred only after 3 months. Our data suggest distinct mechanisms of increased bone turnover in different anticonvulsants. These variable mechanisms may require individual prevention and treatment strategies.

Keywords: Bone turnover; Osteoprotegerin; Oxcarbazepine; RANKL; Valproate.